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Interleukin-4 promotes the clearance of amyloid-β by monocyte through enhancing the recognition and intracellular processing of amyloid-β.

Authors :
Ji, Yi-Fei
Wang, Yan-Jiang
Chen, Si-Han
Cheng, Yuan
Source :
Journal of Alzheimer's Disease. Dec2024, Vol. 102 Issue 4, p1017-1026. 10p.
Publication Year :
2024

Abstract

Background: Impaired clearance of amyloid-β protein (Aβ) in the peripheral system is a crucial event in the pathogenesis of sporadic Alzheimer's disease (AD). Dysfunctional monocytes with deficient clearance of Aβ and increased secretion of pro-inflammatory factors in the periphery are considered to contribute to AD development. Multiple studies suggest that IL-4 can inhibit the inflammatory response and enhance the expression and activity of cathepsin protease associated with intracellular clearance of Aβ by monocytes. Objective: To investigate the effects of interleukin-4 (IL-4) on Aβ clearance and inflammatory response of monocytes in vitro. Methods: In this study, flow cytometry, confocal microscopy and ELISA techniques were used for measurement of Aβ clearance and its related mechanisms of monocytes. Results: We found that the mean intracellular content and uptake ratios of Aβ42 in total monocytes, as well as in the CD14 + CD16− subset, were enhanced by IL-4, concomitant with the degradation of Aβ42 by monocytes. And IL-4 treatment also increased expression of scavenger receptor CD36 and Macrophage scavenger receptor 1 (MSR1) on monocytes. It was shown that IL-4 increased the Aβ immunoreactive area within lysosomal markers, including early endosome antigen 1 (EEA1), lysosome-associated membrane glycoprotein 1 and 2 (LAMP1 and 2) and Aβ degradative enzymes cathepsin B and S in monocytes, but reduced secretion of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interferon-γ (IFN-γ) by monocytes. Conclusions: Our study supports the role of IL-4 in regulating Aβ clearance and inflammatory response by monocytes, suggesting that IL-4 may have therapeutic potential for AD. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
13872877
Volume :
102
Issue :
4
Database :
Academic Search Index
Journal :
Journal of Alzheimer's Disease
Publication Type :
Academic Journal
Accession number :
181908799
Full Text :
https://doi.org/10.1177/13872877241295361